Citation and License

Genome Biology 2004, 5:R97
doi:10.1186/gb-2004-5-12-r97

Published: 30 November 2004

Abstract

Background

Can sequence segments coding for subcellular targeting or for posttranslational modifications
occur in proteins that are not substrates in either of these processes? Although considerable
effort has been invested in achieving low false-positive prediction rates, even accurate
sequence-analysis tools for the recognition of these motifs generate a small but noticeable
number of protein hits that lack the appropriate biological context but cannot be
rationalized as false positives.

Results

We show that the carboxyl termini of a set of definitely non-peroxisomal proteins
with predicted peroxisomal targeting signals interact with the peroxisomal matrix
protein receptor peroxin 5 (PEX5) in a yeast two-hybrid test. Moreover, we show that
examples of these proteins - chicken lysozyme, human tyrosinase and the yeast mitochondrial
ribosomal protein L2 (encoded by MRP7) - are imported into peroxisomes in vivo if their original sorting signals are disguised. We also show that even prokaryotic
proteins can contain peroxisomal targeting sequences.

Conclusions

Thus, functional localization signals can evolve in unrelated protein sequences as
a result of neutral mutations, and subcellular targeting is hierarchically organized,
with signal accessibility playing a decisive role. The occurrence of silent functional
motifs in unrelated proteins is important for the development of sequence-based function
prediction tools and the interpretation of their results. Silent functional signals
have the potential to acquire importance in future evolutionary scenarios and in pathological
conditions.